The purpose of this application is to secure funding to purchase an UltraMicroscope II Light Sheet Fluorescence Microscope (LSFM) for use by multiple investigators with different research disciplines including neural, muscle, and bone biology, collectively called neuromusculoskeletal biology, at the Richard L. Roudebush VA Medical Center (RLR VAMC) at Indianapolis. Neuromusculoskeletal disorders are highly VA-related medical problems, and are urgently unmet medical need. At the RLR VAMC in Indianapolis, strong interactions and collaborations have been established among multiple investigators with expertise in neuromusculoskeletal disorders. With the purchase of the UltraMicroscope II LSFM, which can be used by VA investigators of different disciplines, such collaborations could be further enhanced. The UltraMicroscope II LSFM that we request combines the latest imaging components and proprietary light sheet technologies. This new UltraMicroscope utilizes 6 thin light sheets to excite samples while the fluorescence light is detected with a sCMOS equipped microscope that is mounted perpendicular to the plane illumination. The UltraMicroscope II LSFM serves diverse applications. It delivers superior imaging capabilities and user friendliness. The microscope has been used in different disciplines of biomedical research including neuroscience, developmental biology, immunology, and oncology, and is an idea piece of equipment for multiple PIs investigating neuromusculoskeletal disorders at RRVA. It is an innovative device that overcomes many limitations of currently used conventional approaches and will advance science with high quality, efficiency, precision, and productivity. In this application, two specific aims are proposed. In Aim 1, we describe the purchase and maintenance plan of the UltraMicroscope II LSFM for use by dedicated VA researchers. We have obtained a quotation from the LaVision BioTec for the UltraMicroscope II LSFM. We also discuss the recruitment of Dr. Vance Lemmon, an UltraMicroscope expert, as a consultant on this application. We further discuss the management plan of the UltraMicroscope II LSFM. In Aim 2, we discuss the enhancement of the quality of science and promotion of collaboration among dedicated VA researchers. Over the course of the past 7 years, we have established a strong and dynamic Neuromusculoskeletal research program (NMS) in the Research & Development Service. The UltraMicroscope system represents state-of-the- art light sheet technology for clear tissue imaging and can be applied to neural, muscular, skeletal, and immunological tissue under both normal and pathological conditions. As such, potential acquisition of this system would enhance the current imaging capabilities of our core facilities and allow integrated imaging of NMS tissues from a single animal and across disease states. There is currently no UltraMicroscope II LSFM at the VA or anywhere on the Indiana University School of Medicine (IUSM) campus. Our overall objective with the acquisition of the UltraMicroscope II LSFM is to create new collaborations at RRVA that lead to innovative solutions for health problems facing our veterans. To reach our goal, we have formed a team of 9 investigators, with appointments as Research Scientist, Research Career Scientist, or Senior Research Career Scientist, and each has at least 1 active VA funded grant. Having this novel, state-of-the-art microscope will certainly open up new avenues of research and collaboration at RLR VAMC that would not be possible without it.